1. Field of the Invention
This invention belongs to the field of pharmaceutical chemistry, and provides a new difluoro carbohydrate and new antiviral nucleosides prepared by coupling the new carbohydrate with appropriate bases.
2. State of the Art
It has been known for some time that antiviral drugs can be found among the general family of nucleosides. For example, 5-(2-bromovinyl)-2'-deoxyuridine is known to be a potent agent against herpes virus. DeClercq et al., Proc. Natl. Acad. Sci. U.S.A. 76, 2947-51 (1979). Watanabe et al. have described a number of nucleosides formed by coupling 2-fluoro-2-deoxyarabinofuranose with bases of the cytosine and thymine groups; 5-iodocytosine was their most preferred base. J. Med. Chem. 22, 21-24 (1979), and U.S. Pat. No. 4,211,773.
A compound which can be described as an acyclic nucleoside, 9-(2-hydroxyethoxymethyl)guanine, is a potent antiviral agent, especially useful against herpes viruses, and is the subject of a symposium in a special issue of American Journal of Medicine, July 1982.
Fluorinated carbohydrates have been studied before. A survey of the subject by Penglis is in Advances in Carbohydrate Chemistry and Biochemistry 38, 195-285 (1981). A 2,2-difluorohexose was described by Adamson et al., Carbohydrate Research 18, 345-47 (1971). Wright and Taylor, Carbohydrate Research 6, 347-54 (1968), taught the synthesis of 9-(3-deoxy-3-fluoro-.alpha.-D-arabinofuranosyl)adenine.
Recently the total synthesis of carbohydrates has become the subject of research, and a few papers have appeared. The synthesis requires stereospecific methods, and asymmetric epoxidation and asymmetric aldol reactions have been successfully used. Masamune, Sharpless et al., J. Org. Chem. 47, 1373-81 (1982).